A traditional Chinese medicine composition for treating pulmonary diseases, a preparation method and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating pulmonary diseases and a preparation method and application thereof.The traditional Chinese medicine composition comprises the following raw materials: radix codonopsis, radix astragali, cortex mori, oyster, radix salviae miltiorrhizae, hedyotis diffusae, luffa, angelica sinensis, ligusticum wallichii, persicae semen, earthworm, radix stephaniae tetrandrae, radix peucedani, radices baphlai, kadsurae caudice, radix notoginseng and acanthopanax.The present application is based on the theory of lung-intestine axis, and can improve the clinical symptoms of patients, reduce the levels of IL-1beta, IL-6 and TNF-alpha, regulate the structure of intestinal flora, and has good treatment potential by tonifying qi and tonifying lung, clearing heat and reducing phlegm, promoting blood circulation and dredging collaterals, relieving cough and asthma, and remodeling intestinal flora of patients.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating pulmonary diseases, its preparation method, and its application. Background Technology

[0002] Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by a combination of individual susceptibility factors and environmental factors. It is a preventable and treatable chronic respiratory disease. Currently, there are over 100 million COPD patients in my country, with a prevalence rate as high as 13.7% in people over 40 years old. Occupational dust exposure is a significant environmental factor inducing the onset and progression of COPD, and is also a known cause of silicosis. COPD is a common and serious comorbidity in silicosis patients, and the two diseases influence and promote each other. Therefore, patients with COPD and silicosis experience more severe lung function impairment, a higher risk of acute exacerbations, and significantly impact their quality of life, disease treatment, disease progression, and prognosis, ultimately accelerating death. The gut microbiota, the normal microorganisms in the human gut, synthesizes various essential vitamins and amino acids necessary for human growth and development, and participates in the metabolism of carbohydrates and proteins. It plays a vital role in maintaining human health and is considered an important microecological organ in the human body. The "lung-gut axis" theory confirms that gut microbiota imbalance and its harmful metabolites can affect the lung microenvironment through blood or lymphatic pathways, thereby influencing the development and clinical treatment of lung diseases. This coincides with the classic TCM theory of "the lung and large intestine being internally and externally related." Patients with acute exacerbations of COPD exhibit gut microbiota dysbiosis. Currently, it is believed that beneficial bacteria such as Lactobacillus, Bifidobacterium, Clostridium butyricum, yeast, and Bacillus licheniformis are beneficial bacteria in the gut, which can maintain gut microbiota balance and reduce inflammatory responses by lowering gut-associated inflammatory receptors. Clinical regulation of the gut microbiota mainly relies on probiotic preparations and gut microbiota transplantation. However, for patients with acute exacerbations of COPD and silicosis, the use of antibiotics during treatment can affect the gut microbiota, reducing the efficacy of oral probiotic preparations; secondly, probiotic preparations are often accompanied by adverse reactions such as abdominal distension and constipation; and gut microbiota transplantation faces challenges such as regional microbial inoculation mismatch and the safety of colonoscopy-guided administration. Furthermore, there is currently a general lack of understanding of COPD complications in clinical practice. Treatment for COPD complicated by silicosis remains limited to improving the symptoms of the current acute exacerbation. Specific diagnosis, treatment, and management methods follow those for managing acute exacerbations of COPD, and there is a lack of concrete measures to clearly reduce the risk of future exacerbations. Therefore, there is an urgent need for more effective drugs to reshape the gut microbiota, reduce inflammation levels, and lower the risk of future exacerbations.

[0003] Therefore, this invention is proposed to solve the above-mentioned technical problems. Summary of the Invention

[0004] To address the aforementioned technical problems, the present invention aims to provide a traditional Chinese medicine composition for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis. This composition can help improve lung inflammation, alleviate lung inflammation and pulmonary vascular remodeling by regulating the intestinal flora structure and reducing inflammation levels, thereby achieving the effect of "treating the lung disease by treating the intestines, and treating both the lungs and the intestines simultaneously".

[0005] To achieve the above-mentioned technical effects, the present invention adopts the following technical solution:

[0006] This invention provides a traditional Chinese medicine composition for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Codonopsis pilosula 10-20 parts, Astragalus membranaceus 10-20 parts, Morus alba root bark 5-15 parts, Ostrea gigas 15-25 parts, Salvia miltiorrhiza 20-40 parts, Houttuynia cordata 15-25 parts, Luffa cylindrica 15-25 parts, Angelica sinensis 10-20 parts, Ligusticum chuanxiong 10-20 parts, Prunus persica kernel 5-15 parts, Pheretima aspergillum 5-15 parts, Stephania tetrandra 10-20 parts, Peucedanum praeruptorum 10-20 parts, Stemona japonica 5-15 parts, Gleditsia sinensis thorns 5-15 parts, Curcuma longa 5-10 parts, and Acanthopanax senticosus 3-9 parts.

[0007] According to a preferred embodiment, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts Codonopsis pilosula, 15 parts Astragalus membranaceus, 10 parts Morus alba root bark, 20 parts Ostrea gigas, 30 parts Salvia miltiorrhiza, 20 parts Houttuynia cordata, 20 parts Luffa cylindrica, 15 parts Angelica sinensis, 15 parts Ligusticum chuanxiong, 10 parts Prunus persica, 10 parts Pheretima aspergillum, 15 parts Stephania tetrandra, 15 parts Peucedanum praeruptorum, 10 parts Stemona japonica, 10 parts Gleditsia sinensis thorns, 9 parts Curcuma longa, and 6 parts Acanthopanax senticosus.

[0008] Astragalus, a traditional Chinese medicine, also known as Mianhuangqi, is the dried root of Astragalus membranaceus or Astragalus mongholicus, both belonging to the genus Astragalus in the legume family. It has a sweet taste and slightly warm nature, and enters the spleen and lung meridians. It possesses the functions of strengthening the spleen and replenishing the middle jiao, raising yang and lifting prolapse, benefiting wei qi and consolidating the exterior, promoting diuresis and reducing swelling, and promoting tissue regeneration and detoxification. It is mainly used to treat spleen qi deficiency, lung qi deficiency, and qi and blood deficiency.

[0009] Mulberry bark, a traditional Chinese medicine, is the dried root bark of the mulberry tree (Morus alba) in the Moraceae family after the cork bark has been removed. It is sweet and cold in nature, and enters the lung and spleen meridians. It has the effects of purging lung heat and relieving asthma, promoting diuresis and reducing swelling. Its main functions include: purging lung heat and relieving asthma, promoting diuresis and reducing swelling, tonifying deficiency, promoting blood circulation and removing blood stasis, resolving phlegm and stopping cough, stopping bleeding, promoting body fluid and quenching thirst, purging and relieving constipation, expelling parasites, aiding digestion, dispelling wind, relieving strangury, and relieving pain.

[0010] Oyster, a traditional Chinese medicine. It refers to the shell of oysters such as the Pacific oyster (Crassostrea gigas), the Long oyster (Crassostrea dalianense), or the Dalian Bay oyster (Crassostrea dalianense). Its functions and indications include: astringing yin, suppressing yang, stopping sweating, astringing semen, resolving phlegm, and softening hard masses. It is used to treat epilepsy, dizziness, spontaneous sweating, night sweats, seminal emission, urinary tract infections, metrorrhagia, leukorrhea, scrofula, and goiter. It is also used for palpitations, insomnia, dizziness, tinnitus, scrofula, abdominal masses, spontaneous sweating, night sweats, seminal emission, metrorrhagia, leukorrhea, stomach pain, and acid reflux.

[0011] Salvia miltiorrhiza, a traditional Chinese medicine name. It is the dried root and rhizome of the plant Salvia miltiorrhiza in the Lamiaceae family. It is dug in spring and autumn, removing the sediment and dried. It has the effects of promoting blood circulation to remove blood stasis, dredging meridians to relieve pain, clearing the heart to remove vexation, cooling blood and dissipating carbuncles. It is used for chest pain due to chest impediment, pain in the epigastrium and hypochondrium, mass accumulation, arthralgia due to heat pathogen, restlessness and insomnia, irregular menstruation, dysmenorrhea, amenorrhea, swelling and pain of sores and ulcers.

[0012] Houttuynia cordata, a traditional Chinese medicine name. It is the whole herb with roots of the plant Houttuynia cordata in the Saururaceae family. It belongs to the liver meridian and lung meridian. It has the effects of clearing heat and detoxifying, reducing swelling and treating sores, promoting diuresis and removing dampness, clearing heat and stopping dysentery, strengthening the stomach and promoting digestion. It is used for treating lung abscess, sores and ulcers due to excessive heat, heat-toxin, damp pathogen, dysentery-heat, hemorrhoids with blood in stools, accumulation of heat in the spleen and stomach and other diseases.

[0013] Luffa cylindrica, a traditional Chinese medicine name. It tastes sweet and is slightly cold in nature, belonging to the lung meridian, liver meridian and stomach meridian, and has the effects of expelling wind, dredging collaterals, dissipating nodules, promoting blood circulation and resolving phlegm. It can treat various blood diseases, clear the lung to resolve phlegm and relieve pain on the upper part, soothe the liver and remove stagnation, dredge collaterals and promote lactation in the middle part, and regulate rheumatic arthralgia and heat-toxin carbuncles on the lower part.

[0014] Angelica sinensis, a traditional Chinese medicine name. It is the dried root of the plant Angelica sinensis in the Apiaceae family. It has the effects of enriching blood and promoting blood circulation, regulating menstruation and relieving pain, moistening the intestine and relaxing bowel. It is commonly used for sallow complexion due to blood deficiency, dizziness and palpitation, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency-cold, rheumatic arthralgia, traumatic injury, carbuncles and ulcers, constipation due to intestinal dryness.

[0015] Chuanxiong, a traditional Chinese medicine name. This product is the dried rhizome of the plant Chuanxiong in the Apiaceae family, belonging to the liver, gallbladder and pericardium meridians. It has the effects of promoting blood circulation and regulating qi, expelling wind and relieving pain.

[0016] Peach kernel, a traditional Chinese medicine name. This product is the dried ripe seed of the plant Prunus persica in the Rosaceae family. It has the effects of promoting blood circulation to remove blood stasis, moistening the intestine and relaxing bowel, relieving cough and asthma. It is used for amenorrhea and dysmenorrhea, mass accumulation, lung abscess and intestinal abscess, traumatic injury, constipation due to intestinal dryness, cough and asthma.

[0017] Earthworm, a traditional Chinese medicine name. This product is the dried body of the animal Pheretima vulgaris in the Megascolecidae family. It belongs to the liver, spleen and bladder meridians. It has the effects of clearing heat and relieving convulsion, dredging collaterals, relieving asthma, promoting diuresis. It is commonly used for treating high fever with unconsciousness, infantile convulsion, arthralgia of joints, numbness of limbs, hemiplegia, cough and asthma due to lung heat, oliguria and edema, hypertension and other diseases.

[0018] Stephania tetrandra, a traditional Chinese medicine name. It is the dried root of the plant Stephania tetrandra in the Menispermaceae family. It belongs to the bladder and lung meridians. It promotes diuresis and reduces swelling, expels wind and relieves pain.

[0019] Peucedanum praeruptorum, a traditional Chinese medicine name. It is the dried root of the plant Peucedanum praeruptorum Dunn or Peucedanum decursivum Maxim. in the Apiaceae family. It belongs to the lung meridian. It has the effects of dispersing wind and clearing heat, descending qi and resolving phlegm. It is used for treating wind-heat cough with profuse phlegm, phlegm-heat asthma and fullness, expectoration of thick yellow phlegm and other diseases.

[0020] Stemona root (Bai Bu) is a traditional Chinese medicine. It refers to the dried tuberous root of Stemona japonica, Stemona spp., or Stemona spp., all belonging to the Stemonaceae family. It has the effects of moistening the lungs, relieving cough, and killing parasites and lice. It is commonly used for acute and chronic coughs, pulmonary tuberculosis coughs, and whooping coughs.

[0021] Gleditsia sinensis thorns are a traditional Chinese medicine. They are the dried thorns of the Gleditsia sinensis plant (family Fabaceae). They enter the liver and stomach meridians and have the effects of reducing swelling and promoting pus drainage, and killing parasites. They are commonly used for early-stage carbuncles or boils that have formed pus but have not yet ruptured.

[0022] Turmeric is a traditional Chinese medicine. It has the effects of promoting blood circulation and relieving pain, regulating qi and relieving depression, clearing heat from the heart and cooling blood, and promoting bile secretion and reducing jaundice. It is commonly used for symptoms such as stabbing pain in the chest and ribs, chest pain, amenorrhea and dysmenorrhea, breast distension and pain, delirium due to fever, epilepsy and mania, hematemesis due to blood heat, jaundice and dark urine.

[0023] Acanthopanax senticosus, a Chinese medicine, is a plant of the Araliaceae family. It is pungent, slightly bitter, and warm in nature, and enters the spleen, kidney, and heart meridians. It has the effects of invigorating qi and strengthening the spleen, tonifying the kidney and calming the mind. It is mainly used to treat symptoms such as physical weakness, fatigue, insomnia, and excessive dreaming.

[0024] From the perspective of Traditional Chinese Medicine (TCM), COPD complicated with silicosis falls under the categories of cough, pulmonary distension, and wheezing. It has a slow onset and long course, often due to prolonged exposure to minerals and metals, damaging the body's vital energy (Qi), leading to deficiency of the lungs, spleen, and kidneys. This weakened Qi and weakened defensive Qi result in recurrent lung diseases that trigger the condition. In silicosis patients, the residue of these minerals accumulates in the lungs, impairing lung Qi and disrupting its functions of dispersing and descending Qi. This leads to coughing due to upward Qi flow and wheezing due to impaired ascending and descending Qi, manifesting as difficulty breathing and shortness of breath. Disruption of the pivot mechanism and abnormal Qi movement cause stagnation of lung Qi, which, with prolonged illness, easily leads to internal blood stasis. Furthermore, the *Ling Shu* (Spiritual Pivot) states, "The Lung Meridian of Hand-Taiyin originates in the middle Jiao, descends to connect with the Large Intestine, returns along the stomach opening, ascends through the diaphragm to belong to the Lung," indicating a physiological connection between the lungs and the large intestine. Furthermore, the transmission of lung diseases to the intestines is mentioned in the *Suwen* (Plain Questions) chapter on the Skin: "Therefore, the beginning of all diseases must first occur in the skin and hair. When evil enters, the pores open, and the evil enters the collaterals, lingering and not leaving, then spreading to the meridians, lingering and not leaving, then spreading to the viscera, and accumulating in the stomach and intestines." The *Lingshu* (Spiritual Pivot) chapter on the Four Seasons also states: "There is constant rumbling in the abdomen, qi rushing upwards to the chest, shortness of breath and inability to stand for long, evil in the large intestine." The *Suwen* chapter on the Essential Principles of True Qi states: "Coldness in the intestines rushes upwards to the chest, and in severe cases, shortness of breath and inability to stand for long." This indicates that evil in the large intestine can rise to the chest, affecting the lung's dispersing and descending functions, thus intestinal diseases affecting the lungs and causing lung diseases. Therefore, regulating the intestinal flora and restoring its diversity is of great significance for controlling lung inflammation and reducing the risk of acute exacerbations in patients. This invention targets the symptoms of lung and spleen deficiency, phlegm-heat stagnation, and lung collateral obstruction during the disease process, by supporting the body's resistance and eliminating pathogenic factors, achieving multi-target treatment.

[0025] This invention also provides a medicament for treating pulmonary diseases, comprising a pharmaceutically acceptable carrier and the following raw materials in parts by weight: 10-20 parts Codonopsis pilosula, 10-20 parts Astragalus membranaceus, 5-15 parts Morus alba root bark, 15-25 parts Ostrea gigas, 20-40 parts Salvia miltiorrhiza, 15-25 parts Houttuynia cordata, 15-25 parts Luffa cylindrica, 10-20 parts Angelica sinensis, 10-20 parts Ligusticum chuanxiong, 5-15 parts Prunus persica, 5-15 parts Pheretima aspergillum, 10-20 parts Stephania tetrandra, 10-20 parts Peucedanum praeruptorum, 5-15 parts Stemona japonica, 5-15 parts Gleditsia sinensis thorns, 5-10 parts Curcuma longa, and 3-9 parts Acanthopanax senticosus. The carrier may be, for example, an additive. Preferably, the pharmaceutically acceptable carrier comprises any one or more of the following: flavoring agents, fillers, lubricants, binders, crosslinking agents, pH adjusters, humectants, preservatives, antioxidants, or solvents.

[0026] This invention also provides a method for preparing a traditional Chinese medicine composition, the method comprising:

[0027] S1. Soaking step: Mix the Codonopsis pilosula, Astragalus membranaceus, Morus alba root bark, Oyster shell, Salvia miltiorrhiza, Houttuynia cordata, Luffa cylindrica, Angelica sinensis, Ligusticum chuanxiong, Prunus persica, Salvia miltiorrhiza, Houttuynia cordata, Luffa cylindrica, Angelica sinensis, Ligusticum chuanxiong, Prunus persica, Pheretima aspergillum, Stephania tetrandra, Peucedanum praeruptorum, Stemona japonica, Gleditsia sinensis thorns, Curcuma longa, and Acanthopanax senticosus, and soak in water;

[0028] S2. First decoction step: Add water to the soaked herbs and decoct to obtain the first decoction liquid;

[0029] S3. Second decoction step: Add water to the herbs that have been decocted for the first time and decoct again to obtain the second decoction liquid;

[0030] S4. Mixing step: Mix the first decoction liquid with the second decoction liquid to obtain the traditional Chinese medicine composition.

[0031] Furthermore, in the S1 soaking step, the amount of water used for soaking is sufficient to cover the surface of the herbs, and the soaking time is 45 minutes; further, in the S2 first decoction step, water is added to cover the surface of the herbs by 2-3 cm, and the decoction is carried out by bringing it to a boil over high heat and then simmering over low heat for 30 minutes; further, in the S3 second decoction step, water is added to cover the surface of the herbs by 1 cm, and the decoction is carried out by bringing it to a boil over high heat and then simmering over low heat for 20 minutes.

[0032] One of the objectives of this invention is to provide the application of the above-mentioned traditional Chinese medicine composition in the preparation of products for pulmonary diseases, wherein the pulmonary diseases are chronic obstructive pulmonary disease complicated with acute exacerbation of silicosis.

[0033] Pulmonary function testing is one of the important means of diagnosing COPD. Through pulmonary function testing, a patient's lung ventilation and gas exchange function can be assessed, thereby determining the possibility of airflow limitation and COPD. Simultaneously, pulmonary function testing can also be used to monitor the progression of COPD and the treatment effect, providing important reference for clinical diagnosis and treatment. Pulmonary function tests include FVC (forced vital capacity), FEV1 (forced expiratory volume in one second), and FEV1 / FVC (the ratio of forced expiratory volume in one second to forced vital capacity), all of which are important indicators in pulmonary function testing. Experiments in this invention show that the traditional Chinese medicine composition described in this invention can significantly improve FVC, FEV1, and FEV1 / FVC.

[0034] One of the objectives of this invention is to provide the application of the above-mentioned traditional Chinese medicine composition in the preparation of products that have the functions of reducing the level of inflammation in animal serum and / or regulating the structure of animal intestinal flora.

[0035] In this embodiment of the invention, the product having the function of reducing the level of inflammation in animal serum can reduce the levels of IL-1β, IL-6, and TNF-α in animals.

[0036] Systemic inflammatory response plays a crucial driving role in the pathogenesis and progression of acute exacerbations of chronic obstructive pulmonary disease (COPD) complicated with silicosis, and its levels are closely related to the degree of lung function impairment and the frequency of acute exacerbations. Among these, IL-1β is an early initiator of the inflammatory response, capable of activating downstream inflammatory cascades, playing an important role in both silicosis-related aseptic inflammation and COPD acute exacerbations; IL-6 is a core pro-inflammatory cytokine and acute-phase protein inducer, and its serum levels are positively correlated with systemic inflammatory burden and disease severity; TNF-α is a potent pro-inflammatory mediator that can directly lead to airway inflammation, lung tissue damage, and systemic wasting. Through the interaction of the "lung-gut axis," pulmonary inflammation can exacerbate gut microbiota dysbiosis, while gut-derived inflammatory factors further aggravate systemic and pulmonary inflammation, forming a vicious cycle. Therefore, effectively inhibiting core inflammatory factors such as IL-1β, IL-6, and TNF-α is a key step in controlling systemic inflammation levels and halting disease progression in patients with COPD complicated with silicosis. In this invention, the inflammatory cytokines that the traditional Chinese medicine composition can inhibit include IL-1β, IL-6, or TNF-α. Experiments of this invention show that the traditional Chinese medicine composition can significantly reduce the levels of IL-1β, IL-6, and TNF-α in human or animal serum.

[0037] In this embodiment of the invention, the product having the function of regulating the structure of animal intestinal flora can increase the abundance of Prevotella and / or decrease the abundance of Faecalibacterium in the animal intestine.

[0038] According to a preferred embodiment, the product is a pharmaceutical product.

[0039] The dosage forms of the medicines described in this invention include, but are not limited to, decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays, and / or injections. Capsules are hard or soft capsules, and tablets are oral or dental tablets. Oral tablets refer to tablets intended for oral administration; most of the drugs in these tablets are absorbed through the gastrointestinal tract to exert their effects, while some tablets exert their effects locally in the gastrointestinal tract. Oral tablets include ordinary compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets, or sustained-release tablets.

[0040] The beneficial effects of this invention are:

[0041] This invention relates to a traditional Chinese medicine preparation for treating acute exacerbations of COPD complicated with silicosis. The preparation utilizes a combination of selected herbs including Codonopsis pilosula, Astragalus membranaceus, Morus alba root bark, Ostrea gigas, Salvia miltiorrhiza, Houttuynia cordata, Luffa cylindrica, Angelica sinensis, Ligusticum chuanxiong, Prunus persica, Pheretima aspergillum, Stephania tetrandra, Peucedanum praeruptorum, Stemona japonica, Gleditsia sinensis thorns, Curcuma longa, and Acanthopanax senticosus. Treatment addresses four aspects: tonifying Qi and nourishing the lungs, clearing heat and resolving phlegm, promoting blood circulation and unblocking collaterals, and relieving cough and asthma. It targets external pathogens invading the lungs, phlegm and blood stasis obstructing the lungs, and simultaneously addresses lung Qi deficiency through a combination of tonifying and purging methods. It is convenient to take, addressing both the deficiency of the body's vital energy and powerfully clearing pathological products. Compared to other formulas for treating acute exacerbations of COPD or silicosis, this formula focuses on treating the acute exacerbation phase of COPD complications. It emphasizes both tonifying the body's resistance and eliminating pathogens, with a particular focus on unblocking collaterals and dispersing stagnation, making it a more comprehensive treatment than formulas for single diseases. It is a combination formula that can reshape the patient's gut microbiota and reduce the risk of future attacks. It has the technical advantages of simple formulation, fast effect, strong efficacy and no toxic side effects.

[0042] The composition of this invention can significantly improve lung function in patients with chronic obstructive pulmonary disease (COPD) complicated with acute exacerbations of silicosis in clinical applications. Specifically, it increases forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the FEV1 / FVC ratio, and reduces CAT and mMRC scores. Simultaneously, it effectively reduces the levels of key inflammatory factors IL-1β, IL-6, and TNF-α in the patient's serum and regulates the gut microbiota structure, such as increasing the abundance of beneficial bacteria *Prevotella* and decreasing the abundance of *Faecalibacterium*, significantly improving the community consistency of the gut microbiota and reshaping the gut microecology. Through the "lung-gut axis" mechanism, it can regulate systemic inflammation and immune status, thereby significantly reducing the risk of future acute exacerbations in patients, thus achieving a comprehensive therapeutic effect on acute exacerbations of COPD complicated with silicosis. Attached Figure Description

[0043] Figure 1 Images of PCOA analysis of gut microbiota in patients before and after treatment in Example 5;

[0044] Figure 2 Images showing the changes in the abundance of Prevotella and Megamonas in the intestines of patients before and after treatment in Example 5. Detailed Implementation

[0045] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, those skilled in the art can refer to the content of this document and appropriately improve the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of the present invention.

[0046] In this invention, the term "parts" or "weight parts" refers to the relative mass ratio between related substances, rather than representing the specific mass of a particular substance. Depending on the actual production or clinical situation, one part or one weight part can be 1g, 10g, 500g, 1kg, or any other arbitrary mass.

[0047] The following description is based on specific embodiments.

[0048] Example 1

[0049] This embodiment presents a traditional Chinese medicine composition for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Codonopsis pilosula 10g, Astragalus membranaceus 10g, Morus alba root bark 5g, Ostrea gigas 15g, Salvia miltiorrhiza 20g, Houttuynia cordata 15g, Luffa cylindrica 15g, Angelica sinensis 10g, Ligusticum chuanxiong 10g, Prunus persica kernel 5g, Pheretima aspergillum 5g, Stephania tetrandra 10g, Peucedanum praeruptorum 10g, Stemona japonica 5g, Gleditsia sinensis thorns 5g, Curcuma longa 5g, Acanthopanax senticosus 3g.

[0050] The specific preparation method is as follows:

[0051] Step S1: Soaking. Place the herbs in the above formula into a container according to their weight, add water to cover the herbs, and soak for 45 minutes.

[0052] Step S2: For the first decoction, add water to the soaked medicine to cover the medicine by 2-3cm, bring to a boil over high heat, then simmer over low heat for 30 minutes, and remove the liquid for later use.

[0053] Step S3: Second decoction: Add water to the pot, enough to cover the herbs by 1cm, bring to a boil over high heat, then simmer over low heat for 20 minutes. Remove the liquid and set aside.

[0054] Step S4: Mix the decoction liquid from Step 2 and Step 3 to obtain the final product.

[0055] Example 2

[0056] This embodiment presents a traditional Chinese medicine composition for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Codonopsis pilosula 20g, Astragalus membranaceus 20g, Morus alba root bark 15g, Ostrea gigas 25g, Salvia miltiorrhiza 40g, Houttuynia cordata 25g, Luffa cylindrica 25g, Angelica sinensis 20g, Ligusticum chuanxiong 20g, Prunus persica kernel 15g, Pheretima aspergillum 15g, Stephania tetrandra 20g, Peucedanum praeruptorum 20g, Stemona japonica 15g, Gleditsia sinensis thorns 15g, Curcuma longa 10g, and Acanthopanax senticosus 9g.

[0057] The specific preparation method is as follows:

[0058] Step S1: Soaking. Place the herbs in the above formula into a container according to their weight, add water to cover the herbs, and soak for 45 minutes.

[0059] Step S2: For the first decoction, add water to the soaked medicine to cover the medicine by 2-3cm, bring to a boil over high heat, then simmer over low heat for 30 minutes, and remove the liquid for later use.

[0060] Step S3: Second decoction: Add water to the pot, enough to cover the herbs by 1cm, bring to a boil over high heat, then simmer over low heat for 20 minutes. Remove the liquid and set aside.

[0061] Step S4: Mix the decoction liquid from Step 2 and Step 3 to obtain the final product.

[0062] Example 3: This example describes a traditional Chinese medicine composition for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis. The composition comprises the following raw materials in parts by weight: Codonopsis pilosula 15g, Astragalus membranaceus 15g, Morus alba root bark 10g, Ostrea gigas 20g, Salvia miltiorrhiza 30g, Houttuynia cordata 20g, Luffa cylindrica 20g, Angelica sinensis 15g, Ligusticum chuanxiong 15g, Prunus persica kernel 10g, Pheretima aspergillum 10g, Stephania tetrandra 15g, Peucedanum praeruptorum 15g, Stemona japonica 10g, Gleditsia sinensis thorns 10g, Curcuma longa 9g, Acanthopanax senticosus 6g.

[0063] The specific preparation method is as follows:

[0064] Step S1: Soaking. Place the herbs in the above formula into a container according to their weight, add water to cover the herbs, and soak for 45 minutes.

[0065] Step S2: For the first decoction, add water to the soaked medicine to cover the medicine by 2-3cm, bring to a boil over high heat, then simmer over low heat for 30 minutes, and remove the liquid for later use.

[0066] Step S3: Second decoction: Add water to the pot, enough to cover the herbs by 1cm, bring to a boil over high heat, then simmer over low heat for 20 minutes. Remove the liquid and set aside.

[0067] Step S4: Mix the decoction liquid from Step 2 and Step 3 to obtain the final product.

[0068] Example 4

[0069] The clinical application of the above-mentioned traditional Chinese medicine composition in treating acute exacerbations of COPD complicated with silicosis is as follows:

[0070] (1) General information: Patients who visited the Department of Respiratory Medicine of Henan Provincial People's Hospital from November 2023 to August 2024 were collected. Based on the diagnostic criteria for acute exacerbation of COPD complicated with silicosis, 10 patients who met the diagnosis were selected. All of them were male and the average age was 56.7±6.8 years.

[0071] (2) Inclusion criteria:

[0072] ①40 years old ≤ age ≤ 70 years old;

[0073] ② Meets the diagnostic criteria for COPD as defined by the Global Initiative for COPD (GOLD 2023);

[0074] ③ Meets the diagnostic criteria for silicosis (GBZ70—2009 diagnostic criteria for pneumoconiosis).

[0075] ④ The patient has obvious symptoms of cough, sputum, and shortness of breath;

[0076] ⑤ Sign the informed consent form

[0077] (3) Exclusion criteria:

[0078] ① Patients with concurrent active tuberculosis or malignant lung tumors;

[0079] ② Patients with serious cardiovascular or cerebrovascular diseases, liver or kidney diseases, mental illnesses, or cancer;

[0080] ③ Those who are unwilling to accept research measures or cannot cooperate for other reasons.

[0081] (4) Treatment plan

[0082] All patients used the aqueous extract of the traditional Chinese medicine composition prepared in Example 3, one dose daily, taken twice a day, half an hour after breakfast and dinner. The treatment lasted for three consecutive months.

[0083] (5) Observation indicators

[0084] ①COPD Assessment Test (CAT) score: assesses COPD symptoms, includes 8 items, and has a score range of 0-40. The higher the score, the more severe the symptoms.

[0085] ② Modified UK Medical Research Council Questionnaire (mMRC): Assessing dyspnea symptoms in COPD patients, it correlates well with other indicators reflecting health status and can predict long-term mortality risk;

[0086] ③Inflammatory factors: The levels of IL-1β, IL-6, and TNF-α in the patient's serum were measured before treatment and one month after treatment;

[0087] ④ Intestinal flora: The structure of the intestinal flora of patients was detected before treatment and 3 months after treatment, including the abundance of Prevotella and Faecalibacterium.

[0088] ⑤ Lung function indicators: Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1 / FVC ratio were measured before treatment and 3 months after treatment.

[0089] (6) Detection methods

[0090] ① Cytokine detection process

[0091] Before and one month after administration, 3 ml of fasting peripheral blood was collected from patients using yellow coagulation-promoting tubes. After centrifugation at 3000 rpm for 20 min, the levels of IL-1β, IL-6, and TNF-α in the patients were detected using a fully automated chemiluminescence immunoassay (cytokine kit: light-carrying).

[0092] ② Intestinal flora testing process

[0093] Before and after a 3-month course of medication, 10g of stool samples were collected from the patient using disposable sterile tubes and stored at -80℃. The samples were first extracted using a nucleic acid extraction kit (EZNA). ® The fecal DNA kit (Omega Biotechnology, Georgia, USA) was used to extract fecal DNA from patients according to the instructions of the extraction kit. Electrophoresis was then performed for quality control after extraction. DNA isolated from patient fecal samples was used as a template for PCR amplification of the V3-V4 region of the 16S rRNA gene. PCR amplification was performed using the EasyCycler96 PCR system, with the forward primer (341F) being 5'-CCTACGGGNGGCWGCAG-3' and the reverse primer (805R) being 5'-GACTACHVGGGTATCTAATCC-3'. After amplification, sequencing analysis was performed using the MiSeq sequencing platform (Inmena, USA). The DADA2 algorithm was used to preprocess and quality control the valid sequences of all samples, including removing repetitive sequences, denoising, sequence splicing, generating an amplicon sequence variant (ASV) table, removing chimeras, and finally performing species annotation. Principal coordinates analysis (PCoA) based on Bray-Curtis and unweighted UniFrac distances was performed using R software to display the distances between gut microbiota in different dimensions.

[0094] ③ Lung function testing process

[0095] Using a pulmonary function testing instrument, following the standard operating procedure and explaining the operating instructions to the patient in detail, the patient was asked to sit with a mouth gag in their mouth and cooperate in completing the forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) tests. The FEV1 / FVC ratio was calculated, and each test was repeated 3 times, with the best value recorded.

[0096] (7) Statistical methods

[0097] The data from this experiment were initially compiled and calculated using Excel, and then statistically analyzed and plotted using GraphPadPrism 9.0 software. Quantitative data are expressed as mean ± standard deviation. Paired t-tests were used to compare the pre- and post-treatment data between the two groups. A p-value < 0.05 was considered statistically significant, * indicates p-value < 0.05, and ** indicates p-value < 0.01.

[0098] (8) Results

[0099] ① Comparison of CAT scores before and after treatment

[0100] As shown in Table 1, the CAT score of the patients decreased by 4.9 points after treatment compared with that before treatment, indicating that symptoms such as cough, sputum and wheezing can be improved (P<0.01).

[0101] Table 1 Comparison of CAT scores before and after treatment in patients.

[0102]

[0103] Note: Compared with before treatment, **P<0.01

[0104] ② Comparison of mMRC scores before and after treatment

[0105] As shown in Table 2, the patients' mMRC scores decreased by 0.4 points after treatment compared with before treatment (P<0.05), indicating that the severity of dyspnea can be reduced.

[0106] Table 2 Comparison of mMRC scores before and after treatment in patients.

[0107]

[0108] Note: *P<0.05 compared with before treatment.

[0109] ③ Changes in inflammatory factor markers before and after treatment

[0110] As shown in Table 3

[0111] Table 3 Changes in IL-1β levels before and after treatment in patients.

[0112]

[0113] Note: Compared with before treatment, **P<0.01

[0114] Table 4 Changes in IL-6 levels before and after treatment in patients.

[0115]

[0116] Note: *P<0.05 compared with before treatment.

[0117] Table 5 Changes in TNF-α levels before and after treatment in patients.

[0118]

[0119] Note: Compared with before treatment, **P<0.01

[0120] ④ Changes in the structure and abundance of the gut microbiota before and after treatment

[0121] like Figure 1 As shown, PCOA analysis based on Bray-Curtis distance revealed significant changes in the gut microbiota structure after treatment compared to before treatment. Before treatment, the sample points were scattered in the coordinate space, indicating a disordered gut microbiota structure and low diversity; while after treatment, the sample points were significantly clustered and separated from the pre-treatment sample points, indicating that the gut microbiota structure became more consistent and its diversity improved after intervention with the traditional Chinese medicine composition. This change suggests that the traditional Chinese medicine composition can reshape the gut microbiota and enhance its stability.

[0122] like Figure 2 As shown, the abundance of *Prevotella* spp. in the patient's gut significantly increased after treatment (P<0.05), while the abundance of *Megamonia* spp. significantly decreased (P<0.05). *Prevotella* spp., as beneficial bacteria, contributes to maintaining intestinal barrier function and immune regulation; the decrease in *Megamonia* spp. may be associated with the relief of inflammation. This indicates that the traditional Chinese medicine composition can effectively regulate the gut microbiota structure, promote the growth of beneficial bacteria, and inhibit harmful bacteria, thereby improving lung inflammation and systemic immune status through the "lung-gut axis" mechanism.

[0123] Note: Compared with before treatment, *P<0.05, **P<0.01

[0124] ⑤ Changes in lung function before and after treatment

[0125] Tables 6-7 show the changes in lung function before and after treatment. The FEV1, FVC, and FEV1 / FVC ratio of the patients after treatment were significantly improved compared with those before treatment. This indicates that the traditional Chinese medicine composition of the present invention can effectively improve the lung function of patients with chronic obstructive pulmonary disease complicated with acute exacerbation of silicosis and reduce airflow limitation.

[0126] Table 6. Patients' lung function before treatment

[0127]

[0128] Table 7 Lung function of patients after treatment

[0129]

[0130] Note: Compared with before treatment, **P<0.01

[0131] In summary, this traditional Chinese medicine composition can reduce patients' CAT and mMRC scores, and improve symptoms such as cough, sputum, wheezing, and dyspnea. Simultaneously, it can significantly regulate the levels of inflammatory factors such as IL-1β, IL-6, and TNF-α in serum, maintain the stability of the body's immune system, and regulate the structure of the intestinal flora, increasing the abundance of beneficial bacteria *Prevotella* and decreasing the abundance of *Faecalibacterium*, thus significantly improving the community consistency of the intestinal flora and achieving the remodeling of the intestinal microecology. It can regulate systemic inflammation and immune status through the "lung-gut axis" mechanism, thereby achieving a comprehensive therapeutic effect on acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis.

[0132] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating pulmonary diseases, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: Codonopsis pilosula 10-20 parts, Astragalus membranaceus 10-20 parts, Morus alba root bark 5-15 parts, Ostrea gigas 15-25 parts, Salvia miltiorrhiza 20-40 parts, Houttuynia cordata 15-25 parts, Luffa cylindrica 15-25 parts, Angelica sinensis 10-20 parts, Ligusticum chuanxiong 10-20 parts, Prunus persica kernel 5-15 parts, Pheretima aspergillum 5-15 parts, Stephania tetrandra 10-20 parts, Peucedanum praeruptorum 10-20 parts, Stemona japonica 5-15 parts, Gleditsia sinensis thorns 5-15 parts, Curcuma longa 5-10 parts, Acanthopanax senticosus 3-9 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: Codonopsis pilosula 15 parts, Astragalus membranaceus 15 parts, Morus alba root bark 10 parts, Ostrea gigas 20 parts, Salvia miltiorrhiza 30 parts, Houttuynia cordata 20 parts, Luffa cylindrica 20 parts, Angelica sinensis 15 parts, Ligusticum chuanxiong 15 parts, Prunus persica kernel 10 parts, Pheretima aspergillum 10 parts, Stephania tetrandra 15 parts, Peucedanum praeruptorum 15 parts, Stemona japonica 10 parts, Gleditsia sinensis thorns 10 parts, Curcuma longa 9 parts, Acanthopanax senticosus 6 parts.

3. A method for preparing a traditional Chinese medicine composition according to any one of claims 1 to 2, characterized in that, The preparation method of the traditional Chinese medicine composition includes: S1. Soaking step: Mix the Codonopsis pilosula, Astragalus membranaceus, Morus alba root bark, Oyster shell, Salvia miltiorrhiza, Houttuynia cordata, Luffa cylindrica, Angelica sinensis, Ligusticum chuanxiong, Prunus persica, Pheretima aspergillum, Stephania tetrandra, Peucedanum praeruptorum, Stemona japonica, Gleditsia sinensis thorns, Curcuma longa, and Acanthopanax senticosus, and soak in water; S2. First decoction step: Add water to the soaked herbs and decoct to obtain the first decoction liquid; S3. Second decoction step: Add water to the herbs that have been decocted for the first time and decoct again to obtain the second decoction liquid; S4. Mixing step: Mix the first decoction liquid with the second decoction liquid to obtain the traditional Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that, In the S1 soaking step, the amount of water used for soaking is sufficient to cover the surface of the medicine, and the soaking time is 45 minutes.

5. The preparation method according to claim 3, characterized in that, In the first decoction step of S2, water is added to cover the herbs by 2-3 cm. The decoction is carried out by bringing the herbs to a boil over high heat and then simmering over low heat for 30 minutes.

6. The preparation method according to claim 3, characterized in that, In the second decoction step S3, water is added to cover the herbs by 1 cm. The decoction is brought to a boil over high heat and then simmered over low heat for 20 minutes.

7. The application of a traditional Chinese medicine composition in the preparation of a product for treating acute exacerbations of chronic obstructive pulmonary disease complicated with silicosis, characterized in that, The traditional Chinese medicine composition according to any one of claims 1-2 is used.

8. The application according to claim 7, characterized in that, The product can reduce the levels of IL-1β, IL-6, and TNF-α.

9. The application according to claim 7 or 8, characterized in that, The product can increase the abundance of Prevotella spp. and / or decrease the abundance of Megamonas spp. in the intestine.

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